Emerging Research Issues in Agriculture, Nutrition, Health - Asia and Africa

Sanitation, Mycotoxins, Environmental Enteropathy and

the Gut Microbiome

Prof. Jeffrey K. Griffiths MD MPH&TMDirector, Feed the Future Innovation Laboratory

for Nutrition – AfricaTufts University, Boston USA

Nutrition Interventions – why aren’t they enough?

ADOLESCENT, PRECONCEPTION, GESTATIONAL, AND MATERNAL NUTRITIONADEQUATE CALORIES (PROTEINS, FATS, CARBOS) IN ALL LIFE STAGESDIVERSITY OF MICRONUTRIENTS, VITAMINS, HIGH QUALITY PROTEINSOPTIMAL BREASTFEEDING, RESPONSIVE FEEDING PRACTICES, STIMULATIONGOOD COMPLEMENTARY FEEDING 6-23 MONTHS, DIETARY DIVERSITYWEALTH, EDUCATION – [BE SURE TO CHOOSE YOUR PARENTS WELL] Others…..

PREGNANCY EARLY CHILDHOOD

FIXTHESE:20% OFSTUNTINGAVOIDEDLancet 2013Griffiths Innovation Lb for Nutrition 2

PREGNANCY EARLY CHILDHOOD

MYCOTOXINS: FUNGAL FOOD TOXINS WHICH IMPAIR GROWTH AND IMMUNITY

ENVIRONMENTAL ENTEROPATHY: INFLAMED, LEAKY, DYSFUNCTIONAL INTESTINES THE GUT MICROBIOME - GUT BACTERIA GONE BAD

It’s not just what you eat… It’s your external and internal environment

And how they are linked (water and sanitation)

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MYCOTOXINS IN FOOD

HUMAN AND ANIMAL

PATHOGENS

UNHEALTHYINTESTINAL MICROBIOME

MICRO- AND MACRO-

NUTRIENTS

PERMEABLE (“LEAKY”)AND INFLAMMED GUT

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Drying Cassava, Kamwenge Uganda: note green/yellow fungal discoloration

Photo: J K Griffiths Uganda December 2012 5

FUNGUS GROWING ON CASSAVA

Aflatoxins (Aflatoxins are mycotoxins)

• Produced by Aspergillus fungus• Known – hepatoxic & cause liver cancer in people• Known in mammals to cause growth faltering and

↓ in utero growth (e.g. low birth weight)• Associated* with lower birth weight, growth,

stunting, and wasting in children• Associated* with lower CD4 and higher viral loads

(e.g. worse immunity) in people with HIV• Widespread exposure in sub-Saharan Africa, SE

Asia; maize, peanuts, many other crops.6

*Some criticize these studies for only being “associative” - but it is unethical to give aflatoxinsto people. Prospective studies of exposure and outcomes are needed to show “causation.”

CDC

Gong et al (BMJ, 2002) showed that stunting and weight for age was inversely related to blood aflatoxin levels in Gambia (p < 0.001, R2 =0.37). Jolly et al have shown the same in Ghana.

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Aflatoxins II• Contamination occurs in the field; promoted

by poor (too humid) post-harvest storage.• Passed in utero and in breast milk to children• Complementary food (e.g. porridge made

from maize) is frequently contaminated – as are milk, eggs, chickens, animal meats…

• Prevention: storage without moisture/oxygen; dispersal of natural variant Aspergillus which lacks toxin; test and condemn crops/foods

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High potential for domestic animals and people to contaminate household environment with feces

Photo: J K Griffiths Ethiopia August 2012

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AGRICULTURAL WASTEWATERORGANISM TYPICAL SOURCEROTAVIRUS HUMANS; PERHAPS ANIMALSHEPATITIS A HUMANSHEPATITIS E HUMANS, SWINEE. coli (bacteria) CATTLE, HUMANSShigella species HUMANSSalmonella enterica (bacteria) CATTLE, POULTRY, SWINE, HUMANSCampylobacter jejuni (bacteria) POULTRYCryptosporidium* (protozoan) CATTLE, HUMANS, OTHER FARM ANIMALSMicrosporidia* (fungus) FARM AND DOMESTIC ANIMALS, HUMANS* Causes chronic diarrhea, wasting, malnutrition in people with HIV/AIDSCryptosporidium – a leading cause of diarrhea children < 24 months; known to cause stunting; and children have x 4 risk of death in next year

Pathogens in Rural and Agricultural Water and Watersheds. USDA 2010 10

Poor Sanitation / Hygiene. Fecal Contamination of Domestic Environment

Fecal Ingestion Infants/Children and Enteric Infections

(1) Increased gut permeability (2) Bacteria (and gut contents) leak into body (3) Intestinal Inflammation

ENVIRONMENTAL ENTEROPATHYIn studies dating to 1993, 43% of stunting explained by increased gut permeability

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ENVIRONMENTAL ENTEROPATHY (EE)People living in contaminatedenvironments have leaky, chronically inflamed intestinesEE - Short blunted villi, tissue isinfiltrated with inflammatorycells. 15% less protein and 5%less carbohydrate is absorbed. ↑ nutritional needs, bacteria leak into body, leads to anemia.Bad bacteria are likely cause.

Korpe & Petri, Trends in Molecular Medicine June 2012, Vol. 18, No. 612

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• 317 Malawian twins studied first 3 years of life

• 50% both well nourished; 43% discordant (one well, one malnourished); 7% both were malnourished.

• Both twins in discordant pairs received RUTF, a therapeutic food. Gut microbiomes (MB) studied: RUTF → transient MB improvement.

Science 339:548-554. 1 February 2013

Then…

Improve Don’t Improve

Gnotobiotic (sterile gut) mice – given either Normal or Kwashiorkor MB

Mice given kwashiorkorMB bacteria – lost 1/3 oftheir weight

Mice given normal MB – maintained weight

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Maize, groundnutsKey staple crops

Aspergillus spp. +moisture + warmtemperature =Aflatoxin formation

Aflatoxin ingestion, duodenal uptake -Metabolites bind to DNA, proteins – canmeasure in blood,urine, tissuesImmunosuppression

Diet, Societal Conditions Diet: poor diversity, inadequatecaloric & micronutrient intake, leading to immunosuppression Pathogen exposure: Widespread food, water, environment contamination

Enteropathy – permeable intestine withdocumented increased nutrient needs, state of chronic inflammationMicrobiome – less diverse, abnormalnutrient utilization by flora

Clinical Manifestations:Cycle of repeated infectionsWorsening nutritional status – stunting, underweight, IUGR

Leaky InflamedIntestine (EE)

WASH interventions

Agricultural interventions

Nutrition interventions

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Environmental Enteropathy occurs when people live in contaminated environments. It is reversible. For example, US Peace Corps volunteers develop EE when they live in rural African villages. When they return to the US, their EE goes away. The absence of fecal material – be it human or animal – in the environment both prevents and “treats” EE. Water/sanitation is critical to this separation.• Spears has looked at open defecation as a marker of

sanitation using 140 DHS data sets from 60 countries. How much stunting is due to poor sanitation (and possibly EE?)

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Econometric analyses Spears 2013• Sanitation predicts child height (e.g. stunting) out-

weighing other factors. “…The difference between Nigeria’s 26% open defecation rate and India’s 55% is associated with an increase in child height approximately equivalent to quadrupling GDP per capita.” [open defecation = lack of sanitation]

• Sanitation and population density interact, open defecation harms human capital. Number of people openly defecating explains 65% of international variation in height. The policy case for sanitation as a public good is immense.

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Note going from > 80% without sanitation (far right) to 0% without sanitation moves the HAZ score from under -2 to just under -1. Thus “real world” DHS data analysis suggests a clean environment does lead to decreased stunting.

MYCOTOXINS IN FOOD

HUMAN AND ANIMAL

PATHOGENS

HEALTHY INTESTINAL MICROBIOME

MICRO- AND MACRO-

NUTRIENTS

NORMAL GUT – NOT PERMEABLE

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Solutions• Classic household water & sanitation – water

supply NOT same for animals unless treated; hand-washing; human and animal feces kept out of wastewater to increase food safety.

• Agricultural hygiene – barriers to keep feces out of water - vegetated buffer zones around crops, riparian buffers to slow entry into open water (stream or irrigation canal), manure management, grazing practices …

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Take-Home: healthy growth requires:Adequate, varied nutrition with enough calories,

micronutrients, and vitaminsThe absence of environmental toxins such as aflatoxin

– immunosuppression, poor intra-uterine and post-natal growth, liver toxicity

A clean environment which prevents environmental enteropathy, with its chronic inflammation and higher nutritional needs

A normal gut microbiome which does not starve its host of nutrients and promote weight loss

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